Download A new blueprint for plant pathogen resistance

NEWS AND VIEWS
Heribert Hirt
Heribert Hirt is a professor at the Institute of
Microbiology and Genetics, Vienna Biocenter,
Dr. Bohrgasse 9, A-1030 Vienna, Austria
([email protected]).
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share extensive similarity with insect and
animal receptors (Fig. 1) that are required
for the onset of the innate immune
response and are involved in the sensing of
pathogen-derived factors, called PAMPs
(for pathogen-associated molecular patterns4). Although the defense genes in animals and plants differ considerably, signal
transduction connecting the activation of
Arabidopsis
Mammals
LRR
Every year, a large fraction of worldwide
crop production falls prey to viral, bacterial, or fungal infection. Such infections not
only cause severe losses in world food production, but also can damage human
health by contaminating crops with potent
carcinogens and toxins. Traditionally,
farmers have controlled crop disease
through the application of fungicides and
pesticides, but these chemicals pose environmental and health problems in themselves if used indiscriminately. Genetic
modification allows disease-resistance
traits to be introduced into crop plants,
usually by overexpression of antimicrobial
proteins (e.g., chitinase) or by induction of
key plant defense pathways through signaling molecules (e.g., salicyclic acid, jasmonic acid, or ethylene). A paper published
recently in Nature by Sheen and colleagues1
describes an additional signaling pathway,
the flagellin mitogen-activated protein
kinase (MAPK) cascade, that has considerable potential for the engineering of crops
with broad-spectrum resistance against
fungal and bacterial pathogens.
Plant defense against pathogens is a
complex multistep process including the
expression of an array of defense genes, the
production of a variety of antimicrobial
substances, and programmed cell death at
the site of attack2. In the 1940s, Flor found
in genetic experiments that a single dominant plant disease-resistance locus, R, conferred upon flax plants a resistance to
infection by rust fungus, and that the fungus’ virulence also was dependent on a single fungal gene, Avr (ref. 3). On the basis of
these data, generally summarized by the
“gene-for-gene” concept of incompatible
plant–pathogen interactions, workers set
out to identify the underlying mechanisms.
Many R and Avr genes have now been
identified. Whereas the Avr genes encode a
variety of structurally and functionally different proteins, many plant R proteins
LRR
© 2002 Nature Publishing Group http://biotech.nature.com
A signaling cascade downstream of a leucine-rich repeat receptor
kinase identified in Arabidopsis offers new options for engineering
crop disease resistance.
Receptor
FLS2
TLR2/4/5/9
Plasma
membrane
Kinase
?
IRAK kinase
MAPKKK
AtMEKK1
MEKK
MAPKK
AtMKK4/5
MEK
MAPK
AtMPK3/6
JNK/p38/ERK
Transcription
factor
WRKY22/29
Jun/Fos
Defense gene expression
© Bob Crimi
A new blueprint for plant pathogen resistance
the receptors to the induction of the
defense responses shows some similarities
between kingdoms.
In both animals and plants, kinases of the
MAPKs class are activated by PAMPs.
MAPK pathways are typically multiprotein
complexes containing at minimum a
MAPK, a MAPK kinase (MAPKK), and a
MAPKK kinase (MAPKKK)5. MAPKs are
ideal intracellular mediators of information, because they shuttle between cytoplasm and nucleus, and among their targets
are several classes of transcription factors.
Thus, MAPKs represent the mechanistic
link between information transfer through
the interior of the cell and the transcriptional response in the nucleus.
In their Nature paper, Sheen and colleagues confirm previous studies in various
plant systems, including both monocot6
Figure 1. Model of signal transduction in plants and mammals leading to the expression of defense
genes. In both cases, signaling is initiated by leucine-rich repeat (LRR)–type membrane receptors
that either contain intrinsic kinase activity (e.g., FLS2) or are coupled to cytoplasmic kinases (e.g.,
IRAK). Although signal transduction is mediated through multiple kinase cascades, for simplicity only
the MAPK cascades are shown. At the gene level, expression of defense genes is regulated through
specific transcription factors that are themselves regulated by the MAPKs.
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© 2002 Nature Publishing Group http://biotech.nature.com
NEWS AND VIEWS
and dicot species7–9, demonstrating that
specific MAPKs are involved in pathogen
signaling. Their work combines a transient
expression assay with a genetic approach in
which they identify the FLS2 gene as a
putative sensor of flagellin, a protein from
bacterial flagella. The resulting data place
the MAPKs into register with two closely
related MAPKKs and with a MAPKKK in a
linear pathway downstream of FLS2 (Fig.
1). The targets of the MAPK pathway are
proposed to be two plant-specific transcription factors of the WRKY family.
Confirmation of the biological importance
of this pathway is provided by the fact that
transient
overexpression
of
active
AtMEKK1, AtMKK4, AtMKK5, or one of
the WRKYs confers resistance to
Arabidopsis thaliana leaves upon infection
by the bacterial pathogen Pseudomonas
syringae or the fungal pathogen Botrytis
cinerea1.
What is the biotechnological significance of these findings? R genes are mostly
specific for a certain PAMP and resistance
of host plants is usually lost as soon as the
pathogen sheds or mutates the respective
Avr gene, which frequently occurs due to
the high selection pressure on the
pathogen. The ability to engineer a single
signaling pathway that confers resistance to
various pathogens would therefore be
clearly advantageous, allowing the creation
of crop plants resistant to a wide spectrum
of pathogens in the near future. This can
be achieved either by classical breeding
methods assisted by molecular maker
guidance or by more direct engineering of
crop plants with variants of active
MAPKKKs, MAPKKs, or the WRKY transcription factors.
Before joining in the shouts of joy, we
should consider whether it may be premature to declare the problem completely
solved. Sheen and colleagues have seen
pathogen resistance only in leaves upon
transient overexpression of the active
MAPKKK, MAPKKs and WRKY genes. A
previous report showed that overexpression of active MAPKK in tobacco leaves in
the absence of pathogen attack can lead to
programmed cell death10. Overexpression
of any of these potent regulators might
thus be counterproductive or even lethal.
Moreover, studies in which crop plants
have been engineered for abiotic stress tol-
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erance have shown repeatedly that overexpresssion of stress genes may not be beneficial to the plant but rather may substantially
decrease yield. Several problems therefore
need to be resolved before the procedure
developed by Sheen and coworkers can be
turned into a reliable procedure for generating pathogen-resistant crop plants.
Nevertheless, with increasing concerns
about the environmental and health
impact of fungicides in agriculture, the
availability of a new pathway by which to
engineer pathogen-resistant crops should
be welcome news indeed.
1. Asai, T. et al. Nature 415, 977–983 (2002).
2. Agrios, G.N. Plant Pathology, edn. 4 (Academic
Press, San Diego, 1997).
3. Flor, H.H. Annu. Rev. Phytopathol. 9, 275–296
(1971).
4. Dangl, J.L. & Jones, J.D.G. Nature 411, 826–833
(2001).
5. Hirt, H. (ed.). MAP Kinases in Plant Signal
Transduction (Springer, Heidelberg; 2000).
6. He, C. et al. Mol. Plant Microbe Int. 12, 1064–1073
(1999).
7. Ligterink, W. et al. Science 276, 2054–2057 (1997).
8. Romeis, W. et al. Plant Cell 11, 273–287 (1999).
9. Nühse, T. et al. J. Biol. Chem. 275, 7521–7526
(2000).
10. Yang, K.-Y. et al. Proc. Natl. Acad. Sci. USA 98,
741–746 (2001).
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